tbuckley/cabot-search huggingface dataset:
Enhanced surveillance of hospitalised COVID-19 patients in Europe: I-MOVE-COVID-19 surveillance network, February 2020 to December 2021
Authors: Heather Mutch, Johanna J Young, Fatima Sadiq, Angela MC Rose, Josie MM Evans
Journal: Eurosurveillance (2023)

Background In early 2020, the I-MOVE-COVID-19 hospital surveillance system was adapted from an existing influenza surveillance system to include hospitalised COVID-19 cases. Aim To describe trends in the demographic and clinical characteristics of hospitalised COVID-19 cases across Europe during the first 2 years of the pandemic, and to identify associations between sex, age and chronic conditions with admission to intensive care or high dependency units (ICU/HDU) and in-hospital mortality. Methods We pooled pseudonymised data from all hospitalised COVID-19 cases in 11 surveillance sites in nine European countries, collected between 1 February 2020 and 31 December 2021. Associations between sex, age and chronic conditions, with ICU/HDU admission and in-hospital mortality were examined using Pearson’s chi-squared test, and crude odds ratio (OR) estimates with respective 95% confidence intervals (CI). Results Of 25,971 hospitalised COVID-19 cases, 55% were male, 35% were 75 years or older and 90% had a chronic underlying condition. Patients with two or more chronic underlying conditions were significantly more likely to die in-hospital from COVID-19 (OR: 10.84; 95% CI: 8.30–14.16) than those without a chronic condition. Conclusion The surveillance demonstrated that males, those 75 years or older and those with chronic conditions were at greater risk of in-hospital death. Over the surveillance period, outcomes tended to improve, likely because of vaccinations. This surveillance has laid the groundwork for further research studies investigating the risk factors of hospitalised COVID-19 cases and vaccine effectiveness.
Treatment and outcome of the Dutch Childhood Craniopharyngioma Cohort study: First results after centralization of care
Authors: Jiska Van Schaik, Antoinette Y N Schouten-van Meeteren, Evelien Vos-Kerkhof, Geert O Janssens, Giorgio L Porro, Marta Fiocco, Boudewijn Bakker, Wim J E Tissing, Eelco W Hoving, Hanneke M van Santen
Journal: Neuro-Oncology (2023)

Childhood craniopharyngioma (cCP) has excellent survival, but quality of life may be severely hampered by hypothalamic dysfunction. We aimed to evaluate treatment and hypothalamic outcomes of a Dutch cCP cohort, and evaluate the effect of centralization of care.
Impact of Frontline Ivosidenib on Volumetric Growth Patterns in Isocitrate Dehydrogenase–mutant Astrocytic and Oligodendroglial Tumors
Authors: David Olayinka Kamson, Sushant Puri, Yingying Sang, Meihui Jessica Shi, Lindsay Blair, Jaishri O. Blakeley, John Laterra
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Isocitrate dehydrogenase (IDH)-mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during patients’ most productive years. We report our experience using off-label first-in-class mutant IDH1 inhibitor ivosidenib and its impact on tumor volume in IDH-mutant gliomas. Experimental Design: We retrospectively analyzed patients ages ≥18 years with radiation/chemotherapy-naïve, mutant IDH1, nonenhancing, radiographically active, grade 2/3 gliomas, and ≥2 pretreatment and ≥2 on-treatment ivosidenib MRIs. T2/FLAIR-based tumor volumes, growth rates, and progression-free survival (PFS) were analyzed. log-linear mixed-effect modeling of growth curves adjusted for grade, histology, and age was performed. Results: We analyzed 116 MRIs of 12 patients [10 males, median age 46 years (range: 26–60)]: 8 astrocytomas (50% grade 3) and 4 grade 2 oligodendrogliomas. Median on-drug follow-up was 13.2 months [interquartile range (IQR): 9.7–22.2]. Tolerability was 100%. A total of 50% of patients experienced ≥20% tumor volume reduction on-treatment and absolute growth rate was lower during treatment (−1.2 ± 10.6 cc/year) than before treatment (8.0 ± 7.7 cc/year; P ≤ 0.05). log-linear models in the Stable group (n = 9) showed significant growth before treatment (53%/year; P = 0.013), and volume reduction (−34%/year; P = 0.037) after 5 months on treatment. After treatment, volume curves were significantly lower than before treatment (after/before treatment ratio 0.5; P &amp;lt; 0.01). Median time-to-best response was 11.2 (IQR: 1.7–33.4) months, and 16.8 (IQR: 2.6–33.5) months in patients on drug for ≥1 year. PFS at 9 months was 75%. Conclusions: Ivosidenib was well tolerated and induced a high volumetric response rate. Responders had significant reduction in tumor growth rates and volume reductions observed after a 5-month delay. Thus, ivosidenib appears useful to control tumor growth and delay more toxic therapies in IDH-mutant nonenhancing indolently growing gliomas. See related commentary by Lukas and Horbinski, p. 4709
Promiscuous recognition of MR1 drives self-reactive mucosal-associated invariant T cell responses
Authors: Andrew Chancellor, Robert Alan Simmons, Rahul C. Khanolkar, Vladimir Nosi, Aisha Beshirova, Giuliano Berloffa, Rodrigo Colombo, Vijaykumar Karuppiah, Johanne M. Pentier, Vanessa Tubb, Hemza Ghadbane, Richard J. Suckling, Keith Page, Rory M. Crean, Alessandro Vacchini, Corinne De Gregorio, Verena Schaefer, Daniel Constantin, Thomas Gligoris, Angharad Lloyd, Miriam Hock, Velupillai Srikannathasan, Ross A. Robinson, Gurdyal S. Besra, Marc W. van der Kamp, Lucia Mori, Raffaele Calogero, David K. Cole, Gennaro De Libero, Marco Lepore
Journal: The Journal of Experimental Medicine (2023)

Mucosal-associated invariant T (MAIT) cells use canonical semi-invariant T cell receptors (TCR) to recognize microbial riboflavin precursors displayed by the antigen-presenting molecule MR1. The extent of MAIT TCR crossreactivity toward physiological, microbially unrelated antigens remains underexplored. We describe MAIT TCRs endowed with MR1-dependent reactivity to tumor and healthy cells in the absence of microbial metabolites. MAIT cells bearing TCRs crossreactive toward self are rare but commonly found within healthy donors and display T-helper-like functions in vitro. Experiments with MR1-tetramers loaded with distinct ligands revealed significant crossreactivity among MAIT TCRs both ex vivo and upon in vitro expansion. A canonical MAIT TCR was selected on the basis of extremely promiscuous MR1 recognition. Structural and molecular dynamic analyses associated promiscuity to unique TCRβ-chain features that were enriched within self-reactive MAIT cells of healthy individuals. Thus, self-reactive recognition of MR1 represents a functionally relevant indication of MAIT TCR crossreactivity, suggesting a potentially broader role of MAIT cells in immune homeostasis and diseases, beyond microbial immunosurveillance.
Continuous venetoclax in treatment‐naive <scp><i>TP</i>53</scp> disrupted patients with chronic lymphocytic leukemia: A chronic lymphocytic leukemia campus study
Authors: Andrea Visentin, Francesca Romana Mauro, Lydia Scarfò, Massimo Gentile, Lucia Farina, Gianluigi Reda, Isacco Ferrarini, Giulia Proietti, Enrico Derenzini, Francesca Cibien, Candida Vitale, Alessandro Sanna, Daniela Pietrasanta, Monia Marchetti, Roberta Murru, Gian Matteo Rigolin, Paolo Sportoletti, Valentina Trimarco, Chiara Adele Cavarretta, Francesco Angotzi, Alessandro Cellini, Valeria Ruocco, Ivan Zatta, Luca Laurenti, Stefano Molica, Marta Coscia, Paolo Ghia, Robin Foà, Antonio Cuneo, Livio Trentin
Journal: American Journal of Hematology (2023)

Continuous venetoclax in treatment-naive
A Comparison of Cellular Uptake Mechanisms, Delivery Efficacy, and Intracellular Fate between Liposomes and Extracellular Vesicles
Authors: Timea B. Gandek, Luke van der Koog, Anika Nagelkerke
Journal: Advanced Healthcare Materials (2023)

Abstract A key aspect for successful drug delivery via lipid‐based nanoparticles is their internalization in target cells. Two prominent examples of such drug delivery systems are artificial phospholipid‐based carriers, such as liposomes, and their biological counterparts, the extracellular vesicles (EVs). Despite a wealth of literature, it remains unclear which mechanisms precisely orchestrate nanoparticle‐mediated cargo delivery to recipient cells and the subsequent intracellular fate of therapeutic cargo. In this review, internalization mechanisms involved in the uptake of liposomes and EVs by recipient cells are evaluated, also exploring their intracellular fate after intracellular trafficking. Opportunities are highlighted to tweak these internalization mechanisms and intracellular fates to enhance the therapeutic efficacy of these drug delivery systems. Overall, literature to date shows that both liposomes and EVs are predominantly internalized through classical endocytosis mechanisms, sharing a common fate: accumulation inside lysosomes. Studies tackling the differences between liposomes and EVs, with respect to cellular uptake, intracellular delivery and therapy efficacy, remain scarce, despite its importance for the selection of an appropriate drug delivery system. In addition, further exploration of functionalization strategies of both liposomes and EVs represents an important avenue to pursue in order to control internalization and fate, thereby improving therapeutic efficacy.
Aberrant Vascular Anatomy Associated With Artifactual Focal Avidity in the Liver on PSMA PET
Authors: Ismaheel O. Lawal, Melina Pectasides, Ashwin Singh Parihar, Hardik U. Shah, Raghuveer K. Halkar, Ashesh B. Jani, David M. Schuster
Journal: Clinical Nuclear Medicine (2023)

Abstract 68 Ga–prostate-specific membrane antigen (PSMA) PET/CT is a valuable tool for staging and restaging of prostate cancer. Prostate-specific membrane antigen expression is not specific to prostate cancer, as it is expressed in normal tissues as well as in neoplastic and nonneoplastic processes. Awareness of the broad possibility of lesions with PSMA avidity is necessary to recognize normal variants and avoid potential pitfalls in image interpretation. We present a series of cases showing physiologic focal PSMA avidity in hepatic segment IVb. We correlate this uptake with aberrant hepatic vasculature. The awareness of this variant is important for accurate image interpretation to prevent additional invasive procedures, undue treatment escalation, and denial of curative treatment to patients.
Synchronous Treatment of Breast Cancer Hepatic Metastases by Transarterial Radioembolization and Radiofrequency Thermoablation
Authors: Elisabetta Perrone, Roberto Moretti, Luca Indovina, Roberto Iezzi, Luca Zagaria
Journal: Clinical Nuclear Medicine (2023)

Abstract In a 51-year-old woman affected by breast cancer, hepatic recurrence of disease was managed by concurrent 90 Y-labeled glass microsphere embolization (transarterial radioembolization) and radiofrequency thermoablation. Intention-to-treat target, candidate to radioembolization, was in the IV hepatic segment; another lesion, managed with radiofrequency thermoablation, was in the VI–VII hepatic segment. Concomitant correction of a duodenocephalopancreatic shunting was performed as well. Thermoablation did not interfere with distribution of 99m Tc–macroaggregated albumin and 90 Y-labeled microspheres to the target and healthy liver. At our knowledge, this is the first report that combines 2 locoregional procedures in different hepatic segments on the same day.
FDG Localization in Acellular Dermal Matrix, a Potential Cause of Nonpernicious Uptake Following Breast Reconstruction Surgery
Authors: Gabriel Nemzow, Lionel S. Zuckier
Journal: Clinical Nuclear Medicine (2023)

Abstract A 47-year-old woman with invasive lobular carcinoma of the left breast underwent prophylactic double mastectomy which also incidentally revealed follicular lymphoma of the right breast. Reconstruction was achieved with bilateral silicone implants and acellular dermal matrix (ADM), a biological scaffold material providing mechanical support. Twelve days thereafter, staging PET/CT demonstrated symmetric moderate FDG uptake corresponding to location of the ADM slings, suspected to reflect cellular engraftment onto the ADM and confirmed by near-complete resolution at 3-month follow-up study. FDG uptake related to ADM should be recognized as reflecting expected cellular incorporation into the matrix, rather than recurrent tumor or infection.
Safety, Tolerability, and Antitumor Activity of Zipalertinib Among Patients With Non–Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 20 Insertions
Authors: Zofia Piotrowska, Daniel Shao-Weng Tan, Egbert F. Smit, Alexander I. Spira, Ross A. Soo, Danny Nguyen, Victor Ho-Fun Lee, James Chih-Hsin Yang, Vamsidhar Velcheti, John M. Wrangle, Mark A. Socinski, Marianna Koczywas, John E. Janik, Jeffrey Jones, Helena Alexandra Yu
Journal: Journal of Clinical Oncology (2023)

PURPOSE Although several agents targeting epidermal growth factor receptor ( EGFR ) exon 20 insertions (ex20ins) have recently been approved by the US Food and Drug Administration, toxicities related to the inhibition of wild-type (WT) EGFR are common with these agents and affect overall tolerability. Zipalertinib (CLN-081, TAS6417) is an oral EGFR tyrosine kinase inhibitor (TKI) with a novel pyrrolopyrimidine scaffold leading to enhanced selectivity for EGFR ex20ins-mutant versus WT EGFR with potent inhibition of cell growth in EGFR ex20ins-positive cell lines. METHODS This phase 1/2a study of zipalertinib enrolled patients with recurrent or metastatic EGFR ex20ins-mutant non–small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. RESULTS Seventy-three patients were treated with zipalertinib at dose levels including 30, 45, 65, 100, and 150 mg orally twice a day. Patients were predominantly female (56%), had a median age of 64 years, and were heavily pretreated (median previous systemic therapies 2, range 1-9). Thirty six percent of patients had received previous non-ex20ins EGFR TKIs and 3/73 (4.1%) patients received previous EGFR ex20ins TKIs. The most frequently reported treatment-related adverse events of any grade included rash (80%), paronychia (32%), diarrhea (30%), and fatigue (21%). No cases of grade 3 or higher drug-related rash or diarrhea were observed at 100 mg twice a day or below. Objective responses occurred across all zipalertinib dose levels tested, with confirmed partial response (PR) observed in 28/73 (38.4%) response-evaluable patients. Confirmed PRs were seen in 16/39 (41%) response-evaluable patients at the dose of 100 mg twice a day. CONCLUSION Zipalertinib has encouraging preliminary antitumor activity in heavily pretreated patients with EGFR ex20ins-mutant NSCLC, with an acceptable safety profile, including low frequency of high-grade diarrhea and rash.
The NHS at 75: love, and political consensus, is all you need
Authors: Kamran Abbasi
Journal: BMJ (2023)

The NHS is 75 years old.It is damaged, demoralised, and distracted.It is also loved.By some accounts, love is all you need.And if love weren't enough, the magic dust of the founding principles sprinkle the NHS with the aura of a religion too.To meet the needs of everyone, to be free at the point of delivery, and to be based on clinical need, not ability to pay, are principles that have endured-although some interested parties are eager to erode them.Love and religion make the headiest cocktail.
Wip1 inhibits neutrophil extracellular traps to promote abscess formation in mice by directly dephosphorylating Coronin-1a
Authors: Yifang Chen, Chenxu Zhao, Han Guo, Weilong Zou, Zhaoqi Zhang, Dong Wei, Hezhe Lu, Lianfeng Zhang, Yong Zhao
Journal: Cellular and Molecular Immunology (2023)
Tumor Volume on PSMA PET as a Prognostic Biomarker in Prostate Cancer Patients Treated With Cabazitaxel
Authors: Qaid Ahmed Shagera, Ioannis Karfis, Spyridon Sideris, Thomas Guiot, Erwin Woff, Nieves Martinez-Chanza, Thierry Roumeguere, Thierry Gil, Patrick Flamen, Carlos Artigas
Journal: Clinical Nuclear Medicine (2023)

The aim of this study was to evaluate the prognostic value of 68 Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in metastatic castration-resistant prostate cancer patients receiving second-line chemotherapy with cabazitaxel.All patients with metastatic castration-resistant prostate cancer who underwent a PSMA PET/CT within 8 weeks before initiating the cabazitaxel treatment were retrospectively evaluated. The whole-body PSMA total tumor volume (PSMA-TV) was measured for each patient. Other factors such as prostate-specific antigen, hemoglobin, lactate dehydrogenase, and alkaline phosphatase were recorded. A log-rank cutoff finder was used to define the PSMA-TV optimal cutoff. Survival analyses were performed using Cox regression and Kaplan-Meier methods.In total, 32 patients were included, receiving a median of 6 cycles of cabazitaxel (range, 2-10). After a median follow-up of 12 months, 28 patients presented disease progression, and 18 died. Baseline PSMA-TV presented a significant association with progression-free survival (PFS) and overall survival (OS; P = 0.035 and P = 0.002, respectively). Optimal PSMA-TV cutoffs were 515 mL for PFS and 473 mL for OS. Patients with low volume presented longer PFS and OS than those with high volume: median PFS, 21 versus 12 weeks, respectively (hazard ratio, 0.33; P = 0.017); and median OS, 24 versus 8.5 months, respectively (hazard ratio, 0.21; P = 0.002). On the multivariable analyses, PSMA-TV remained an independent predictor of OS ( P = 0.016).Our results show that total tumor volume measured on PSMA PET/CT is a prognostic biomarker in patients treated with cabazitaxel. High PSMA-TV before treatment initiation is associated with shorter PFS and OS.
18F-FDG PET/CT Imaging Findings of a Case of Primary Cardiac Chondrosarcoma and Pulmonary Inflammation
Authors: Yi-Ting Liu, You Cheng, Dan Shao
Journal: Clinical Nuclear Medicine (2023)

Abstract Primary cardiac chondrosarcoma invading the right pulmonary vein is very rare, whereas secondary cardiac chondrosarcoma is relatively common. We reported the 18 F-FDG PET/CT findings of primary cardiac chondrosarcoma and pulmonary inflammation misdiagnosed as cardiac malignancy and pulmonary metastasis in a 27-year-old man.
Novel Diagnostic Imaging Approach for Patients With Spontaneous Coronary Artery Dissection
Authors: Zaid N. Safiullah, Jacqueline M. Latina, Efthymios Ziogos, Tarek Harb, Thomas H. Schindler, Ines Valenta-Schindler, Abass Alavi, Gary Gerstenblith, Thorsten M. Leucker
Journal: Clinical Nuclear Medicine (2023)

Spontaneous coronary artery dissection (SCAD) is an underdiagnosed etiology of acute coronary syndrome in women. Accurate diagnosis remains challenging but is imperative for treatment and prevention. We show here the utility of 18 F-FDG PET imaging in SCAD diagnosis. We present 1 representative case of 4 women with suspected SCAD on coronary angiography from the EVACS (Evolocumab in Acute Coronary Syndromes) clinical trial. 18 F-FDG PET imaging showed acute inflammation in the distribution of the suspected dissected coronary artery identified on angiography. Localized myocardial inflammation identified on 18 F-FDG PET imaging can aid in diagnosing SCAD suspected on coronary angiography.
Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report
Authors: Muhammad M Mohiuddin, Avneesh K Singh, Linda Scobie, Corbin E Goerlich, Alison Grazioli, Kapil Saharia, Claire Crossan, Allen Burke, Cinthia Drachenberg, Cihan Oguz, Tianshu Zhang, Billeta Lewis, Alena Hershfeld, Faith Sentz, Ivan Tatarov, Sarah Mudd, Gheorghe Braileanu, Kathryn Rice, John F Paolini, Kent Bondensgaard, Todd Vaught, Kasinath Kuravi, Lori Sorrells, Amy Dandro, David Ayares, Christine Lau, Bartley P Griffith
Journal: The Lancet (2023)
Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies
Authors: Giacomo Cozzi, Laura Scagnellato, Mariagrazia Lorenzin, Edoardo Savarino, Fabiana Zingone, Francesca Ometto, Marta Favero, Andrea Doria, Stephan R. Vavricka, Roberta Ramonda
Journal: Nature Reviews Rheumatology (2023)
Mendelian randomization evidence for the causal effects of socio-economic inequality on human longevity among Europeans
Authors: Chao-Jie Ye, Li-Jie Kong, Yi-Ying Wang, Chun Dou, Jie Zheng, Min Xu, Yu Xu, Mian Li, Zhi-Yun Zhao, Jie-Li Lu, Yu-Hong Chen, Guang Ning, Wei-Qing Wang, Yu-Fang Bi, Tian-Ge Wang
Journal: Nature Human Behaviour (2023)
Single-cell multi-omics of mitochondrial DNA disorders reveals dynamics of purifying selection across human immune cells
Authors: Caleb A. Lareau, Sonia M. Dubois, Frank A. Buquicchio, Yu-Hsin Hsieh, Kopal Garg, Pauline Kautz, Lena Nitsch, Samantha D. Praktiknjo, Patrick Maschmeyer, Jeffrey M. Verboon, Jacob C. Gutierrez, Yajie Yin, Evgenij Fiskin, Wendy Luo, Eleni P. Mimitou, Christoph Muus, Rhea Malhotra, Sumit Parikh, Mark D. Fleming, Lena Oevermann, Johannes Schulte, Cornelia Eckert, Anshul Kundaje, Peter Smibert, Santosha A. Vardhana, Ansuman T. Satpathy, Aviv Regev, Vijay G. Sankaran, Suneet Agarwal, Leif S. Ludwig
Journal: Nature Genetics (2023)
Tom Nolan’s research reviews—29 June 2023
Authors: Tom Nolan
Journal: BMJ (2023)

SurreyTranexamic acid after major trauma "It is hard to imagine that doctors or paramedics would withhold a treatment that saves lives in the short term because survivors may be severely disabled at six months," say the authors of an editorial linked to new research.A randomised trial set in Australia recruited 1310 adults with major trauma who had a high risk of trauma induced coagulopathy according to the seven-point COAST score.Six months after prehospital treatment with tranexamic acid or placebo, there was no difference in survival with a favourable outcome (moderate to no disability) between the two arms of the trial (53.7% v 53.5% respectively).A secondary outcome of death at 28 days found a benefit from tranexamic acid: 17.3% versus 21.8%.
The recombinome of IKZF1 deletions in B-cell precursor ALL
Authors: Bruno A. Lopes, Claus Meyer, Heloysa Bouzada, Marius Külp, Ana Luiza Tardem Maciel, Patrizia Larghero, Thayana C. Barbosa, Caroline P. Poubel, Caroline Barbieri, Nicola C. Venn, Luciano Dalla Pozza, Draga Barbaric, Chiara Palmi, Grazia Fazio, Claudia Saitta, Thais F. Aguiar, Mecneide M. Lins, Maura R. V. Ikoma-Colturato, Marcia Schramm, Eduardo Chapchap, Gianni Cazzaniga, Rosemary Sutton, Rolf Marschalek, Mariana Emerenciano
Journal: Leukemia (2023)